PROJECT SUMMARY The objective of our competing renewal application for the Univ of Chicago Research Training Program in Respiratory Biology is to prepare young scientists to pursue research careers addressing mechanisms and treatment of human disease, with a focus on respiratory pathobiology. The cohesiveness of this interdiscipli- nary Program stems from the highly collaborative nature of our 38 well-funded faculty in 7 departments and the Institute for Molecular Engineering at the Univ of Chicago in multiple areas of concentration. Studies in Asthma and Airway Physiology/Immunology continue to focus on airway inflammation, airway smooth muscle and epithelial structure and function, B-cell and T-cell activation, asthma genetics, and clinical investigation. These complement programs of Studies in Lung Immunology and Transplantation that focus on cellular and molecular mechanisms underlying transplantation immunology and their translational applications to patients, and translational Studies in Interstitial Lung Diseases that draw on one of the largest dedicated clinics in the Midwest. A Concentration in Airway and Mucosal Microbiome adds this critically important emerging research direction to the asthma and ILD programs. Studies in Critical Illness and Acute Lung Injury continue to address subcellular determinants of oxygen sensing and consumption, cellular responses to hypoxia, membrane biology, endothelial and epithelial barrier function, and bedside translations to patients with sepsis, cardiopulmonary arrest, and sleep disturbance. Complementing these are cross-cutting Studies in Genetics and Epigenetics and Concentration in Health Studies and Ethics. The Program Directors are Anne I. Sperling, PhD and Julian Solway, MD, with Associate Director Steven White, MD (Mentorship and Career Development). Christopher Olopade, MD, MPH chairs a Diversity Committee. Internal and External Advisors provide oversight and continuity of review, and an Admissions/Steering Committee reviews trainee progress. We request funding for 10 post-doctoral trainees. PhD, MD, and MD/PhD trainees are enrolled and trained together. Collaboration of basic and clinical scientists on research further enhances the integrative and translational nature of our program. All fellows perform full-time research for at least 2 years, and MD fellows will devote not more than 10% time to clinical training while supported by this Program. Training consists of 5 major components: a Research Project performed under the direct supervision of faculty co-mentors; a Core Curriculum of robust seminar series and courses with additional, tailored formal coursework; Core Competencies that includes scientific communication, grant writing, and mentoring; Multidisciplinary Research; and Individualized Career Development Planning. Prior trainees from this Program have developed successful independent research careers in large proportion. Refinements presented here should further enhance the likelihood for success of future trainees.